Slide Scanner with a Tilted Image

Abstract

An instrument and method for scanning a large microscope specimen uses a light source and at least one lens to focus light from the specimen onto a detector array. The specimen holder is located on a scanning stage and the detector array is dynamically tilted about a scan direction during the scan to maintain focus across the width of the scan strip as the scan proceeds. A degree of tilt varies during the scan as is required to maintain lateral focus relative to the detector array.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]This invention relates to the fields of microscopic imaging of large specimens with particular emphasis on brightfield and fluorescence imaging. Applications include imaging tissue specimens, genetic microarrays, protein arrays, tissue arrays, cells and cell populations, biochips, arrays of biomolecules, detection of nanoparticles, photoluminescence imaging of semiconductor materials and devices, and many others.[0003]2. Description of the Prior Art[0004]Several technologies are used for imaging large specimens at high resolution. Tiling microscopes record an image of a small area of the specimen using a digital camera (usually a CCD camera), the specimen is moved with a computer-controlled microscope stage to image an adjacent area, an image of the adjacent area is recorded, the stage is moved again to the next area, and so on until a number of image tiles have been recorded that together cover the whole area of the sp...

AI Technical Summary

Benefits of technology

This patent describes a method and instrument for scanning large microscopic specimens on glass slides using a linear detector array that can be tilted during scanning to maintain focus across the entire width of the scan strip. The instrument and method can also be used for fluorescence imaging and 2D detector arrays. Additionally, the patent explains how to measure the focus and tilt needed to maintain focus during scanning. The technical effect is to provide a more efficient and accurate way to scan and analyze large microscopic specimens.

Problems solved by technology

Such images may contain tiling artifacts caused by different focus positions for adjacent tiles.

For large specimens, thousands of tiles may be required to image the entire specimen, requiring many changes in focus which increase the chances of tiling artifacts.

When a CCD-based TDI array is used, each line image stored in memory is the result of integrating the charge generated in all of the previous lines of the array while the scan proceeds, and thus has both increased signal / noise and amplitude (due to increased exposure time) when compared to the result if a linear array detector were used.

If the specimen is not flat, or the specimen is tilted about the scan direction, proper focus may not be achieved across the whole width of the strip.

In addition, focus at the edge of adjacent strips may be different, making it difficult to stitch image strips together to assemble a complete image of the specimen without focus mismatch at the edge of strips.

These problems are made worse when magnification is increased (which decreases depth of field) and when the width of the scan strip on the specimen is increased.

Images